Silencing the Long Non-coding RNA HOTAIR Inhibits Epithelial-Mesenchymal Transition in MKN45 Gastric Cancer Cell Line by Downregulation of Fibronectin-1 and Claudin-4

 Gastric cancer is one of the most prevalent human malignancy-related death worldwide, which is usually diagnosed at the advanced stages resulting in metastasis. Recent studies have revealed that long non-coding RNAs (lncRNAs), which are known as non-coding RNAs, play a significant role in creating variety of molecular pathways (e.g., growth, proliferation, differentiation, and apoptosis) and negatively contribute to many unusual processes, including human cancers. The HOX antisense intergenic RNA (HOTAIR) is one of the novel non-coding RNAs which has recently emerged as a promoter of metastasis in different types of human cancers through epithelial-to-mesenchymal transition (EMT) process. Epithelial-to-mesenchymal transition (EMT) is a cellular process where an epithelial cell could change its phenotype to mesenchymal condition, which plays a crucial role in promoting cell invasion, angiogenesis, and metastases.

 This study aimed to explore the effect of HOTAIR gene silencing on the expression levels of two main markers of EMT signaling pathway, fibronectin (FN1) and claudin4 (CLDN4) in MKN45 cellular model of gastric cancer. The MKN45 cells were subjected to HOTAIR specific siRNA for 48 hours, and the extracted RNAs were subjected to cDNA synthesis and real-time PCR. The expression change was calculated using 2-ΔΔct.

 Our findings showed that FN1 and CLDN4 were upregulated in MKN45 cells. Following the transfection of cell by HOTAIR siRNA, both FN1 and CLDN4 genes were significantly downregulated.

 HOTAIR long non-coding RNA may have regulated the expression levels of FN1 and CLDN4 genes in EMT signaling pathway. However, it was recommended that further experimental analyses should be carried out to confirm this observation. In other word, our study result may not have been applied as a therapeutic access until additional experiments were conducted.